Chest
Volume 101, Issue 2, February 1992, Pages 350-355
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Clinical Investigations
Failure of Inhaled Corticosteroids to Modify Bronchoconstrictor or Bronchodilator Responsiveness in Middle-Aged Smokers with Mild Airflow Obstruction

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We have compared the effects of three-month periods of treatment with an inhaled corticosteroid, budesonide 600 µg twice daily and with placebo on bronchial responses to inhaled histamine and to bronchodilators in a double-blind crossover trial in 14 middle-aged male smokers (mean age, 59.6 years) with mild airways obstruction (mean FEV1 2.42 L, SO percent predicted [range, 48 to 110 percent]). Responsiveness to inhaled histamine was assessed monthly by the provocative concentration (mg/ml) reducing FEV1 by 20 percent (PC20). Bronchodilator response to a combination of inhaled salbutamol (5 mg) and ipratropium (0.5 mg) was assessed before and after three months' treatment. Compliance with treatment was checked by weighing aerosol canisters, and by measuring plasma budesonide and metabolites. There was no significant change in FEV1 (budesonide mean 2.38 L [SEM 0.17] vs placebo 2.40 L [0.17]), vital capacity (budesonide mean 3.69 L [0.17] vs placebo 3.81 L [0.17]) or in bronchodilator responsiveness (mean increase over baseline FEV1, budesonide 11.6 [2.7] percent vs placebo 10.5 [3.2] percent). There was a small overall reduction in bronchoconstrictor responsiveness over the period of the trial, but there was no effect of 12 weeks of budesonide treatment compared with 12 weeks of placebo treatment (mean log PC20 during budesonide 0.505 [SEM 0.063], placebo 0.591 [SEM 0.055]). Following the three-month crossover trial, six men continued for nine more months to receive budesonide in a single-blind trial and the results were compared with those in six men who took no active treatment for the subsequent nine months. No improvements in baseline spirometry, home peak flow measurements, bronchoconstrictor or bronchodilator responsiveness were observed after 12 months of budesonide treatment. Thus, a regimen of budesonide treatment that consistently attenuates bronchial responsiveness in asthmatic subjects had no effect in these men; larger and longer trials will be required to establish whether a subgroup of smokers shows a favorable response.

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Subjects

Fifteen middle-aged male smokers with measurable BHR to inhaled histamine without overt asthmatic features were recruited from those attending a long-term follow-up study of the effects of smoking started in 1974;15 their rate of change in FEV1 over the preceding 12 years was therefore known. At initial recruitment and at subsequent follow-up, all men were encouraged to give up smoking. These men were found to have BHR to inhaled histamine in 1982.16 In that study the majority of smokers,

Double-Blind crossover Trial

Smoking Habits: These were generally similar through the trial (as assessed by stated habits and FECO); one patient unsuccessfully tried to quit smoking for a few days during the trial.

Compliance with Treatment: In the 14 men who completed the trial, canister weights showed a reduction averaging 0.37 g/day with most individuals showing similar values; qualitative measurements of plasma budesonide also confirmed the presence of budesonide in all the men at the end of the appropriate 12-week

DISCUSSION

In the present study we were unable to demonstrate any consistent improvement in baseline lung function, home peak flow, bronchoconstrictor responsiveness, or bronchodilator responsiveness in smokers with mild airflow obstruction following three months of treatment with budesonide. These results contrast with the consistent improvement others have found with similar treatment in patients with asthma,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 but agree with two other recent studies in smokers with

ACKNOWLEDGMENTS

This work was supported by grants from the Medical Research Council and Chest, Heart and Stroke Association, and some further financial assistance from A.B. Draco. We are grateful to Vic Aber and Robert Robinson for help with the statistical analysis.

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